The inhibitor of I kappa B alpha phosphorylation BAY 11-7082 prevents NMDA neurotoxicity in mouse hippocampal slices.

NF-kappaB is a nuclear transcription factor involved in the control of fundamental cellular functions including cell survival. Among the many target genes of this factor, both pro- and anti-apoptotic genes have been described. To evaluate the contribution of NF-kappaB activation to excitotoxic insult, we analysed the effect of IkappaBalpha (IkappaBalpha) phosphorylation blockade on glutamate-induced toxicity in adult mouse hippocampal slices. By using immunocytochemical and EMSA techniques, we found that (i) acute exposure of hippocampal slices to NMDA induced nuclear translocation of NF-kappaB, (ii) NMDA-mediated activation of NF-kappaB was prevented by BAY 11-7082, an inhibitor of IkappaBalpha phosphorylation and degradation, and (iii) BAY 11-7082-mediated inhibition of NF-kappaB activation was associated with neuroprotection.

Neuroprotection by metabotropic glutamate receptor agonists on kainate-induced degeneration of motor neurons in spinal cord slices from adult rat.

Research has provided evidence about the role of excitotoxicity in the pathophysiology of sporadic amyotrophic lateral sclerosis and suggests that AMPA/kainate receptor activation contributes greatly in mediating glutamate injury to motor neurons. The recent finding of variable expression of metabotropic glutamate (mGlu) receptor subtypes in adult rat spinal cord has prompted us to investigate their contribution to the excitotoxic process. We report here that stimulation of mGlu receptors efficiently prevents motor neuron degeneration induced by kainate. The application of kainate to lumbar spinal cord slices from adult rats induced a massive degeneration of motor neurons which became shrunken, dark and TUNEL-positive. On the contrary, no significant neurotoxicity was observed after NMDA application. A blockade of ionotropic non-NMDA receptors by CNQX, and mGlu receptor stimulation, efficiently counteracted kainate-mediated cell death. Among the various agonists for mGlu receptors, we tested 3-hydroxyphenylglycine (3HPG), which selectively stimulates group I mGlu receptors. In addition, we tested 2-(carboxycyclopropyl)glycine (L-CCG-I) and 4-carboxy-3-hydroxyphenylglycine (4C3HPG), two selective agonists for group II receptors, as well as L-amino-4-phosphonobutyrate (L-AP4), a preferential agonist for group III. The results suggest that all three groups of mGlu receptors are involved in inhibiting excitotoxic phenomena mediated by kainate on spinal cord motor neurons. This was despite being localized differently and, possibly, activating different neuroprotective pathways.

The role of surgery in the treatment of primary gastric lymphoma.

The present retrospective study of 23 patients with primary gastric lymphoma had the objective of determining the role of surgical treatment on survival. All patients were submitted to gastric resection with regional lymph node removal. Nine patients (39.1%) received supplementary treatment (chemotherapy and/or radiotherapy). According to the Kiel classification, the most frequent histological type was the centroblastic (29.1%), and most patients (60.9%) had a low-grade lymphoma. According to the Ann Arbor classification, modified by Musshoff and Schmidt-Vollmer, stages were IE in 52.1%, II1E in 8.7%, II2E in 13.1%, and IV in 26.1% of the cases. Mean survival was 29.3 months. The variables that influenced survival rates were age, advanced stage tumor, and receiving postoperative adjuvant therapy. Analysis of our cases suggests that complete lesion resection along with adjacent lymph nodes, and supplementary postoperative treatment is the best approach for a resectable primary gastric lymphoma.

Interleukin-1beta and glutamate activate the NF-kappaB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures.

We originally reported that members of the family of transcription factors NF-kappaB/Rel can specifically recognize two identical sequences, referred to as APPkappaB sites, which are present in the 5'-regulatory region of the APP gene. Here we show that the APPkappaB sites interact specifically with a complex which contains one of the subunits of the family, defined as p50 protein, and that they act as positive modulators of gene transcription in cells of neural origin. Additionally, the nuclear complex specifically binding to the APPkappaB sites is constitutively expressed in primary neurons from rat cerebellum and it is up-regulated in response to both the inflammatory cytokine interleukin-1beta (IL-1beta) and the excitatory amino acid glutamate. Since IL-1, whose levels are known to be induced in brain of individuals affected by Alzheimer's disease, and glutamate, are stimuli which have been regarded as major actors on the stage of neurodegenerative processes, we believe our evidence as potentially relevant for understanding the neuropathology associated with Alzheimer's disease.

Restaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase staining of CEA and cytokeratins.

The present study was performed to identify tumor cells in lymph nodes from colorectal adenocarcinomas considered free of disease by the classic hematoxylin-eosin stain, based on the detection of the carcinoembryonic antigen (CEA) and cytokeratins in neoplastic epithelial cells. For this purpose, 603 lymph nodes from 46 lesions were stained by the peroxidase-antiperoxidase technique. Tumor cells were detected in 22 nodes from 12 patients, mainly in the subcapsular sinuses, permitting a restaging of these patients into two groups: those now considered to have metastatic disease and those free of metastases. However, the 5-year follow-up showed no statistical differences in survival between the two groups.

[Effects of parenteral nutrition on tumor growth: experimental aspects]. / Efeitos da nutrição parenteral sobre o desenvolvimento tumoral: aspectos experimentais.

There still exist controversies about the effect of parenteral nutrition on cancer growth. For elucidation of this question the development of Walker 256 carcinosarcoma in rats submitted to parenteral nutrition (PN) was studied. Thirty-five Wistar rats were randomly distributed in three groups: OT group (11), tumor-bearing animals always under oral feeding for 14 days; PC group (14), tumor free animals under PN for 7 days; PT group (10), tumor-bearing rats under PT for 7 days. PT solution contained 15% glucose, 3% aminoacids and essential micronutrients. Body and tumor weight (in OT and PT groups) were evaluated daily. Carcass weight was obtained by the difference between the body and tumor weight. The rats of the PC group had an initial body weight loss that became stabilized afterwards at a lower plateau level. The rats of the PT group also presented an initial body weight loss recovered progressively afterwards. This difference is probably due to tumor mass expansion in PT animals, since PT rats carcass weight remained similar to that of body weight in PC group. The tumor growth has shown no difference between the oral and parenteral feeding groups, particularly when tumor weight/carcass weight ratio was considered. It is concluded that parenteral nutrition does not favor tumor growth in detriment to carcass weight development.

An experimental study of the impact of cancer on nitrogen metabolism and wound healing.

In Wistar rats bearing a Walker-256 carcinoma flank tumor, a standard skin wound was inflicted on the backs of the animals. Nitrogen intake and nitrogen balance measures were obtained. The standard wound did not promote tumor growth. Wound contraction in tumor-bearing animals was not different from that in tumor-free animals. Tumor-bearing rats had anorexia, lower nitrogen intake and a tendency to lower their nitrogen balance. These findings suggest that both cancer and wound healing are privileged metabolic events, having as a consequence sacrifice of the host.

[Body composition changes in cancer: an experimental study]. / Alterações da composição corpórea no câncer: estudo experimental.

With the aim to study body composition changes in tumor bearing rats submitted to different nutritional conditions, Wistar rats were separated in three diet groups: regular chow, aproteic diet and regular chow after three weeks of aproteic diet. Afterwards the animals were divided in two subgroups: Waler 256 carcinossarcoma bearing rats and tumor free controls. After the sacrifice body composition measurements by the carcass analysis method were performed. Tumor bearing rats presented significant waste of total body fat, body cell mass and increase of Na/K ratio without relation to the nutritional regimen. From this data we conclude that Walker 256 carcinosarcoma causes protein caloric malnutrition even in already depleted rats. After adequate refeeding, body composition rebuilding was obtained in tumor bearing malnourished rats.

[Influences of antitumoral chemotherapy on body composition and nitrogen balance: experimental study]. / Conseqüências da quimioterapia antitumoral sobre a composição corpórea e o balanço nitrogenado: estudo experimental.

An experimental study was carried out with the purpose to examine the 4-epidoxorubicine (4-EPI) action on malignant tumor development and its repercussion on nutritional conditions of the host. Cancer and chemotherapy can generate malnutrition. In order to study the nutritional repercussions, 48 host Wistar rats were divided into 5 groups: Group C: 12 control rats; Group T: 5 rats bearing Walker-256 carcinosarcoma; Group TE: 11 rats given 4-epidoxorubicine (4-EPI) EV simultaneously with tumor implantation; Group T6E: 8 rats given 4-EPI 6 days after the tumor implantation; Group E: 11 rats given only 4-EPI. Tumor and carcass weight and nitrogen balance (by measuring total nitrogen ingested and excreted) were determined daily; the animals were sacrificed on the 20th day of the experiment and material was collected for determination of body composition parameters. A variance analysis was made and the differences were considered to be significative at p less than 0.05. A loss of food during a period following the 4-EPI injection was reflected by carcass weight loss. The accumulated nitrogen incorporation was lower in Groups TE and T6E in the periods of 0-5 days, 0-14 days, and 0-20 days. As for body composition it was verified that free fat solids and total body fat were reduced in Groups T ant T6E when compared to group C. However, 20 days after the use of 4-EPI there were no significative changes in the body composition. In rats bearing Walker-256-carcinosarcoma 4-EPI was effective.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gastric epithelioid leiomyoma (leiomyoblastoma). Analysis of a case and review of the literature]. / Leiomioma epitelióide gástrico (leiomioblastoma). Análise de um caso e revisão da literatura.

The authors report a case of gastric epithelial leiomyoma (leiomyoblastoma). Macroscopically, such tumors resemble leiomyoma, with a biological behavior between leiomyoma and leiomyosarcoma. A review of the medical literature indicates that gastrointestinal bleeding is the most usual manifestation. Gastrointestinal seriography and endoscopy are the most utilized diagnostic exams. The endoscopic biopsy, many times, is unable to confirm the malignant or benign nature of the tumor. It is emphasized the importance of identifying the potentially malignant tendency of the tumor, indicated, mainly, by histology and mitotic counting. The treatment is surgical and consists of local or gastric resection, according to the neoplastic localization, its extension, infiltration, biological nature and the presence of multiple tumors. In the case reported, the patient was operated in urgency because of hemoperitoneum and the source of bleeding was a neoplastic vessel in the anterior wall of the antrum, which was not resected at that time. Later on, a biopsy of the gastric tumor performed during a routine surgery disclosed the real nature of the disease. Once the histopathological diagnostic was made and its potential malignant evolution detected the patient was re-operated. A partial gastrectomy with removal of the antrum was performed. Now, the patient has been asymptomatic with no evidences of metastasis after 30 months of the diagnostic.

Bacteriologia da bile em afeccoes litiasicas das vias biliares.Associacao clinico-radiologica. / Biliary bacteriology in cholelithiasis. Clinical and radiological aspects

Os autores realizaram estudos bacteriologicos de amostras biliares de 55 pacientes submetidos a cirurgia das vias biliares extra-hepaticas devido a colecistopatias litiasicas cronicas e agudas. Relacionaram dados clinicos e radiologicos pre e intra-operatorios com a presenca de bacteriobilia. Obtiveram taxas de positividade de 34,5% para bacterias aerobias e 20% para anaerobias. A analise estatistica dos dados clinicos e bacteriologicos apresentou significancia com relacao a existencia de ictericia, febre, diagnostico de patologia aguda e colangiografia operatoria anormal.Nao houve associacao com o tempo de historia clinica ou com o achado radiologico pre-operatorio

[Bacteriology of the bile in cholecystopathies. Radiological association]. / Bacteriologia da bile em colecistopatias. Associação radiológica.

A clinicobacteriological survey was undertaken in 55 patients undergoing biliary surgery, because of chronic and acute cholecystitis. Some radiological preoperative and operative aspects were analised in order to detect any relation of these aspects with biliary tract infection. The bile cultures were positive in 34,5% and 20,0% for aerobes an anaerobes microorganisms respectively. The microorganisms most frequently isolated were Escherichia coli, Pseudomonas aeruginosa, Klebsiella, Bacteroides sp and Clostridium sp, as aerobian and anaerobian. The statistical analysis showed significance between the presence of bacteria in the biliary tract and pathological operative cholangiography. It had not significance with the radiological preoperative aspects.

Uma experiencia de ensino em tecnica cirurgica na Faculdade de Medicina da Universidade de Sao Paulo. / A teaching experience in surgical technic at the University of Sao Paulo Medical School

Os autores analisam inicialmente o sentido de que deve revestir-se o processo educacional, salientando a importancia que assume o planejamento do conteudo e a definicao previa de criterios de avaliacao. Examinam a seguir a evolucao da disciplina MCG-610 - Estagio Hospitalar em Tecnica Cirurgica, do curso de graduacao da Faculdade de Medicina da USP.Verificam que, embora a avaliacao da disciplina pelos estudantes tenha melhorado no periodo considerado, a sistematica de avaliacoes adotada permite entrever uma possivel perda de qualidade no desempenho da disciplina. Outros elementos referentes ao curso medico desenvolvido na instituicao sao tambem analisados